Pathogenesis of gastrointestinal symptoms
Intestinal involvement has many reasons. The angiotensin-converting-enzyme 2 receptor (ACE-2) and transmembrane protease, serine 2 (TMPRSS2), are key proteins in the cellular entry process of the virus. The co-expression of these two proteins in the same cell is essential for the entry of SARS-CoV-2.13Like the type II alveolar cells in the lung, the glandular cells of the gastric, duodenal and rectal epithelium, and the enterocytes of the ileum and colon can express both proteins at a high level. The esophageal epithelium expresses ACE-2 at a lower level. ACE-2 is also expressed on the surface of hepatocytes, and to a greater extent, on the surface of cholangiocytes.
Although the specific mechanisms involved in diarrhea’s pathogenesis are not fully understood, the infection is likely to alter intestinal permeability, with malabsorption by enterocytes. Furthermore, ACE-2 has been proposed to be involved in the absorption of dietary amino acids, regulating the expression of antimicrobial peptides, and promoting homeostasis of the intestinal microbiome. The mouse model know-out for ACE-2 frequently develop colitis subsequently to SARS-CovV-2 infection, suggesting that the virus may cause enzymatic changes, increased susceptibility to intestinal inflammation and diarrhea.
Further studies are needed to clarify the mechanisms underlying diarrhea and to define the correlation between respiratory and gastrointestinal symptoms. The virus also appears to alter the intestinal microbiome even when only the respiratory mucosa is involved through the regulation of the mucosal immune system (the ”gut-lung axis”).4